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Learning Scope #420
1 contact hour
Expires Feb. 11, 2015

The prevalence of current and emerging multidrug resistant organisms (MDRO) pose ongoing threats to both young and old alike, increasing morbidity and mortality while straining the healthcare delivery system. The combination of consistent preventive measures, antimicrobial stewardship and education offer the best options to stem the mounting danger.

Since 1995, the prevalence of MDRO has increased by more than 300 percent, prompting the CDC to declare a national priority for government and scientific leadership.¹ Current and emerging organisms compound prevention measures and tax an encumbered surveillance system.

Not long after the introduction of methicillin in the 1960s, the new superbug to healthcare - methicillin-resistant Staphylococcus aureus (MRSA) - emerged, which became one of the first well-known MDROs. MRSA accounted for nearly 53 percent of all Staphylococcus aureus isolates from patients with nosocomial infections in 2000 and increased to 59 percent in 2003.²

But this was just the beginning. Healthcare facilities soon identified multidrug resistant (MDR) Acinetobacter baumannii, vancomycin-resistant Enterococcus (VRE), and MDR Pseudomonas aeruginosa. Military medical facilities also reported increases of up to 55 percent of MDRO-associated respiratory infections.³ Nationally, organisms such as these and others are estimated to cause thousands of deaths annually and add billions of dollars in healthcare costs.

Patients of all ages can be affected by MDROs; however, colonization within long-term care facilities poses additional risks to the elderly and others, and add a resource burden as up to 10 percent of infected hospitalized individuals are admitted from these facilities.⁴ Additionally, facilities with chronically ill patients may demonstrate more MDRO catheter-associated blood stream infections and catheter-associated urinary tract infections than high-acuity ICUs.⁵

Along with the increase in MDROs, healthcare facilities face new challenges with the emergence of pan-resistant organisms (those resistant to all drugs) that further complicate patient treatment and outcomes, and add to the complexity of managing outbreaks.⁶

Infection prevention methods and surveillance plays a key role in managing these organisms, from community-acquired cases to outbreaks. The implications for healthcare providers are tremendous. As antimicrobial resistance escalates, the result becomes a race for improved tools and production of new antibiotics to combat these costly and deadly organisms.⁷

Virulence is composed of various characteristics that include the favored site of invasion, ability to cause disease, immunity or avoidance to host defense mechanisms, and acquisition of nutrients from the host environment.⁸

For instance, microorganisms continually subjected to antimicrobial therapies can increase in virulence through mutation-causing resistance to their host environment. If not controlled, the resulting mutated changes become more detrimental to future hosts. Virulence can be affected by different factors, including the microorganism's ability to survive in the external environment between transmission from host to host.⁹

Pathogens may prefer specific environments. For instance, Pseudomonas is a common "water bug" preferring an aqueous environment that it can inhabit for months.⁹ Clostridium difficile is a hearty spore highly resistant to chemical agents, heat and drying conditions, which allows it to survive for months in the environment supporting germination into an active form after invading its host.⁹

Transmission to a new host - an important factor of virulence - can occur from a variety of mechanisms. There are insect vectors, such as the mosquito, which can carry West Nile virus from host to host or ticks that transmit Lyme disease from the pathogen Borrelia burgdorferi.⁹ Some viruses can live in the environment and be transferred to the mucous membranes of a susceptible host after touching contaminated surroundings, such as a patient's hospital room. Escherichia coli and other bacteria possess motility, allowing it to swim upstream in flowing urine from a Foley catheter bag to the bladder, causing infection.⁹ In fact, 80 percent of microorganisms possess some form of motility, allowing them to adapt and survive in favored environments.⁸

Although preventable, healthcare-acquired infections (HAI) are the most common complication of hospitalization and one of the top 10 leading causes of death. The Agency for Healthcare Research and Quality (AHRQ) estimates the cost of HAI runs $28 billion to $33 billion annually.¹⁰ Increased education on MDRO and preventive measures can help reduce this financial burden as well as improve patient outcomes.

The emergence of pan-resistant organisms has caused great concern in healthcare and public health systems, specifically the carbapenem resistance in Enterobacteriaceae, otherwise known as CRE. Infections with CRE are difficult to treat, commonly resulting in a 40-50 percent mortality rate.¹¹ Patients infected with CRE who are moved through various healthcare settings, such as long-term to acute care, often spread the organism between facilities.¹¹ Hospital-wide outbreaks of CRE are costly, devastating to patients and challenging to control.

Carbapenem antibiotics are the last line of defense when combating life-threatening infections.¹² The most commonly identified CRE organism to cause concern within a healthcare setting is carbapenem-resistant Klebsiella pneumoniae (KPC).¹² KPCs are highly resistant to all antibiotic classes and have high mortality rates in chronically ill patients, in particular those exposed to invasive devices such as mechanical ventilators or central venous catheters.¹³ Patients with CRE often contaminate their environment, allowing for increased potential of transmission to healthcare workers' hands and, subsequently, patients.¹⁴

Acinetobacter baumannii has been linked with HAIs including pneumonia, bacteremia, urinary tract and wound contamination.¹⁵ A. baumannii survives for long periods of time in the patient's environment and displays highly virulent features, making it difficult to eradicate. As with other MDROs, patients at risk for infection include those requiring mechanical ventilation, multiple antibiotic use, surgery or invasive procedures and increased length of stays in an ICU.¹⁵ A. baumannii also is prevalent in rehabilitation and long-term care facilities, favoring chronically ill patients with an increased underlying severity of illness.¹⁵ Similar to CREs, A. baumannii poses a threat to the general public health due to the transfer of rehab and long-term care facilities patients to hospitals, thus increasing the risk of transmission throughout a variety of healthcare settings.¹⁵

Extended-spectrum beta-lactamases (ESBLs) are enzymes that display resistance to certain classes of antibiotics which include cephalosporins and monobactams.¹⁶ Commonly seen ESBLs include Klebsiella pneumoniae, Escherichia coli and Klebsiella oxytoca.¹⁶ The increased prevalence of ESBLs has threatened the healthcare system with limited availability of antibiotics for treatment which may result in higher mortality rates. While not as resistant as CREs, ESBLs complicate care, increase lengths of stay in acute settings and are common causes of urinary tract and blood stream infections.

Clostridium difficile, the leading cause of infectious diarrhea within the healthcare setting, continues to show an increased incidence rate, mortality and severity. Despite prevention measures, Clostridium difficile infection (CDI) remains at historically high rates with nearly 14,000 deaths annually due to the infectious diarrheal disease, according to the CDC.¹⁷ CDI may be prevented through judicious use of antibiotics.

The Society for Healthcare Epidemiology of America (SHEA) recommends clinicians minimize the frequency and duration of antimicrobial therapy and implement a stewardship program with restrictions on cephalosporin and clindamycin.¹⁸ With as many as half of all prescribed antibiotics deemed unnecessary, the incidence of CDI could be drastically decreased.¹⁸

Growing evidence also suggests that proton pump inhibitors (PPI) may be correlated to CDI. One recent study at a community hospital identified nearly 65 percent of patients with CDI also were prescribed a PPI either prior to hospitalization or during their stay.¹⁹

Interestingly, once thought of as a predominantly HAI, Clostridium difficile now is displaying a trend in the public setting with nearly a third of all cases originating from within the community environment.²⁰ Based on a recent study in the American Journal of Gastroenterology investigating prevalence and risk factors, hospital-acquired CDI demographically favored elderly adults while community-acquired CDI occurred in younger, predominantly female adults.²⁰

The study also identified that the risk factors for healthcare-acquired vs. community-acquired CDI varied as well, demonstrating that healthcare-acquired CDI had an estimated 94 percent antibiotic use 90 days prior to infection with more severe cases than community-acquired. Community-acquired CDI cases were associated with less antibiotic usage and lower comorbidity factors than healthcare-acquired.²⁰ These factors create an opportunity for additional research to investigate causation and improvement in treatment options.

One of the most common causes of healthcare-associated bacteremia, Staphylococcus aureus, also is commonly associated with skin and wound infections due to its endogenous nature for skin colonization.²¹ MRSA is associated with increased risk of infection, morbidity and mortality among hospitalized patients. Although invasive MRSA HAIs have been declining, education and prevention methods are necessary to support improved patient outcomes. Conversely, community-acquired MRSA infections continue to increase and commonly present as skin infections.²²

The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant Staphylococcus aureus (VRSA) within the healthcare community pose a growing threat to patients. Fortunately, these infections often can be treated with antibiotics and are not as frequently seen in the U.S. as compared to the rest of the world.²³ VRE are Enterococci organisms resistant to vancomycin. Enterococci is a common gastrointestinal organism in humans and also is present in the genitourinary tract in females.²⁴

These organisms are commonly associated with healthcare-acquired urinary tract infections.²⁵ Chronically ill patients and those exposed to several treatments of antibiotics are more prone to VRE infections. This problem underscores the importance of judicial antibiotic use and prevention methods in the chronically ill patient population.²⁴

Nurses are the first line of defense in preventing HAIs. As bedside caregivers, nurses have an important role in halting the transmission of these organisms among patients. Nurses ensure staff adherence to contact precautions and hand hygiene, educate physicians and ancillary employees, advocate for improved patient outcomes and protect the care environment. Organisms such as Clostridium difficile require aggressive hand hygiene with soap and water while use of alcohol-based gel or foam may suffice for others. Understanding the virulence and prevalence of MDROs is an important first step in the line of defense to prevent transmission.

Carbapenem-resistant Enterobacteriaceae outbreaks can be difficult to control, highlighting the importance of prevention methods. The CDC recommends aggressive infection prevention measures that should include: active surveillance to identify CREs within the healthcare setting, strict contact precautions and adherence to hand hygiene, education for healthcare personnel, minimizing the use of invasive devices, antimicrobial stewardship, cohorting CRE patients colonized or actively infected, screening and daily bathing with chlorhexidine gluconate.¹¹ CRE screening may help identify patients at risk for developing infection, such as the chronically ill admitted from long-term care facilities and/or those admitted to high-risk settings such as the ICU.¹¹

Patients colonized with CRE also can be a source of transmission, so identifying those individuals upon admission, with immediate placement into contact precautions could prevent the spread to other immunocompromised or susceptible people.¹³ With limited treatment options available, monitoring susceptibilities and resistance with cultures and prevention measures helps control further transmissions. Supporting the patient's hemodynamic, ventilatory, fluid and nutritional status, while controlling other comorbid conditions, often is the most appropriate option for care.

According to research in Infection Control and Hospital Epidemiology, healthcare workers' hands examined after caring for patients with MDR A. baumannii and MDR P. aeruginosa, were frequently contaminated with MDR A. baumannii. Additionally, the organism also was present on gowns, gloves and unwashed hands.²⁶ Their results showed MDR A. baumannii could be more easily transmitted than MDR P. aeruginosa and perhaps even more so than MRSA or VRE.²⁶

Although the researchers found ease of transmission specific to A. baumannii, these results emphasize the importance of adhering to contact precautions and hand hygiene for all healthcare workers. A. baumannii can survive on surfaces for extended periods of time, underscoring the importance of thorough environmental cleaning programs at all healthcare facilities.¹⁵ Prevention is only as effective as the consistent use of policies and processes in place to control infectious organisms.

The past several decades have brought on the emergence of new MDROs. However, with a decline in the development of new and effective antimicrobial therapies, antibiotic stewardship programs can identify the best therapies while aiming to achieve optimal clinical outcomes.² Resistant organisms must be combated at a faster rate because of dramatic increases in morbidity, mortality and healthcare costs. With limited or no available treatment for some infections, antibiotic stewardship incorporates concepts such as surveillance to identify trends, detection of newly emerging MDROs, their susceptibility patterns and prevention of transmission.²

Antimicrobial stewardship programs incorporate interventions to ensure patients receive the correct antibiotic with the "right" dose at the "right" time and for the "right" duration. Organizations should incorporate specific measurement methods with the ability to monitor ways in which healthcare facilities perform tasks (i.e., administer antibiotics, etc.) and address outcomes to improve effectiveness. Monitoring cost, Clostridium difficile infection rates, adverse drug events and emerging resistant pathogens in the healthcare setting are components of a program with defined metrics to meet specific stewardship goals and are endorsed by the CDC.²

A joint position paper released in early 2012 by SHEA, Infectious Disease Society of America (IDSA) and Pediatric Infectious Diseases Society (PIDS) recommends public policy around antimicrobial stewardship for regulation and widespread participation.² Highlights of the release include regulation over antimicrobial stewardship programs and mandates from Centers for Medicare and Medicaid for participating hospitals.² The recommendations encouraged all levels of healthcare facilities to implement antimicrobial stewardship programs with multidisciplinary teams that include a physician, pharmacist, microbiologist and infection preventionist.¹⁰

It is just as important for ambulatory care centers to monitor antibiotic use as in acute care settings. With the growing prevalence of MDROs and CDI in the community, monitoring for optimal use of antibiotics in outpatient settings could prevent further emergence.² Education, data and research also are essential pieces to stewardship programs. With significant knowledge deficits of antimicrobial stewardship among healthcare workers, increased research, data and widespread education should be incorporated into annual competencies and formal education programs.²

In addition to medication use, environmental factors may be responsible for the transmission of infections, specifically CDI. A hearty spore that can survive in the environment for an estimated six months or more, Clostridium difficile is highly resistant to alcohol and routine hospital disinfectants. The CDC recommends the use of a 1:10 hypochlorite (bleach) solution to kill Clostridium difficile spores from the patient environment.¹⁷

Furthermore, strict contact precautions and adherence to a hand hygiene program decrease the transmission of CDI among hospitalized patients. With soap and water being the preferred hand hygiene method for removing the spores, screening of high-risk individuals and staff education is necessary to identify patients with confirmed or potential CDI so that vigilance with proper precautions can be maintained.¹⁸

As with any preventive measures, hand hygiene remains the No. 1 method to prevent the transmission of infections both within healthcare settings as well as in the community. Nurses remain at the forefront of infection control and adherence to defined methods of prevention by educating patients and families on the simple aspects of care such as hand hygiene.

Easily accessible hand hygiene gel or foam dispensers in patient care environments and education on their use can support the family's need to help care for their loved one. Education pamphlets can reinforce and clarify information.

MDROs are increasing in prevalence. Obstacles to control and prevention measures must be utilized in the community and healthcare settings to decrease the risk of MDROs and CDI transmission. With the emergence of pan-resistant organisms and the tremendous implications for public health and the healthcare system, practicing strict isolation precautions and hand hygiene programs, educating bedside caregivers and implementing antimicrobial stewardship programs, the potential to reduce the incidence and save lives is achievable.

References
1. Scheans P. Clinical challenges: is your nursery full of MDROs? Neonatal Netw. 2010;29(6):392-395.
2. Fishman N, Patterson J, Saiman L, et al. Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infect Control Hosp Epidemiol. 2012;33(4):322-327.
3. Keen EF, Murray CK, Robinson BJ, et al. Changes in the incidences of multidrug-resistant and extensively drug-resistant organisms isolated in a military medical center. Infect Control Hosp Epidemiol. 2010;1(7):728-732.
4. Chitnis A, Edwards J, Ricks P, et al. Device-associated infection rates, device utilization, and antimicrobial resistance in long-term acute care hospitals reporting to the national healthcare safety network, 2010. Infect Control Hosp Epidemiol. 2012;33(10):993-1000.
5. O'Fallon E, Vicas A, & D'Agata E. The emerging threat of multidrug-resistant gram-negative organisms in long-term care facilities. J Gerontol. 2009;64(1):138-141.
6. Marchaim D, Chopra T, Bogan C, et al. The burden of multidrug resistant organisms on tertiary hospitals posed by patients with recent stays in long-term acute care facilities. Am J Infect Control. 2012;40(8):760-765.
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8. Casadevall A, & Pirofski L. Virulence factors and their mechanisms of action: the view from a damage-response framework. J Water Health. 2009;7(Suppl 1):S2-S18.
9. Carrico R. (Ed). Association for Professionals in Infection Control Text of Infection Control and Epidemiology. Washington, DC: Association for Professionals in Infection Control and Epidemiology; 2012.
10. Moody J, Cosgrove S, Olmsted R, et al. Antimicrobial stewardship: a collaborative partnership between infection preventionists and health care epidemiologists. Am J Infect Control. 2012;40(2):94-95.
11. CDC. 2012 CRE Toolkit: Guidance for Control of Carbapenem-Resistant Enterobacteriaceae (CRE). 2012. Available at: http://www.cdc.gov/hai/organisms/cre/cre-toolkit. Accessed Jan. 21, 2013.
12. Schwaber M, Lev B, Israeli A, et al. Containment of a country-wide outbreak of carbapenem-resistant klebsiella pneumoniae in Israeli hospitals via a nationally implemented intervention. Clin Infect Dis. 2011;52(7):848-855.
13. CDC. Guidance for Control of Infections with Carbapenem-Resistant or Carbapenemase-Producing Enterobacteriaceae in Acute Care Facilities. 2009. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5810a4.htm. Accessed Jan. 21, 2013.
14. Lerner A, Adler A, Abu-Hanna J, et al. Environmental contamination by carbapenem-resistant enterobacteriaceae. J Clin Microbiol. 2013;51(1):177-181.
15. Maragakis L & Perl T Acinetobacter baumannii: epidemiology, antimicrobial resistance and treatment options. Clin Infect Dis. 2008;46(8):1254-1263.
16. CDC. Laboratory Detection of Extended-Spectrum β-lactamases (ESBLs). 2012. Available at: http://www.cdc.gov/HAI/settings/lab/lab_esbl.html. Accessed Jan. 21, 2013.
17. CDC. Clostridium difficile. 2012. Available at: http://www.cdc.gov/HAI/organisms/cdiff/Cdiff_clinicians.html. Accessed Jan. 21, 2013.
18. Cohen S, Gerding D, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2012;31(5):431- 455.
19. Bengualid V, Umesh K, Alapati J, et al. Clostridium difficile at a community hospital in the Bronx, New York: incidence prevalence and risk factors from 2006 to 2008. Am J Infect Control. 2011;39(3):183-187.
20. Khanna S, Pardi D, Aronson S, et al. The epidemiology of community-acquired Clostridium difficile: a population-based study. Am J Gastroenterol. 2012;107(1):89-95.
21. Loomba P, Taneja J, & Mishra B. Methicillin and vancomycin resistant S. aureus in hospitalized patients. J Glob Infect Dis. 2010;2(3):275-283.
22. CDC. MRSA Statistics. 2012. Available at: http://www.cdc.gov/mrsa/statistics/index.html. Accessed Jan. 21, 2013.
23. CDC. CDC Reminds Clinical Laboratories and Healthcare Infection Preventionists of Their Role in the Search and Containment of Vancomycin-Resistant Staphylococcus aureus (VRSA). 2012. Available at: http://www.cdc.gov/HAI/settings/lab/vrsa_lab_search_containment.html. Accessed Jan. 21, 2013.
24. CDC. Vancomycin-resistant Enterococci (VRE) in healthcare settings. 2012. Available at: http://www.cdc.gov/HAI/organisms/vre/vre.html. Accessed Jan. 21, 2013.
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Resource
CDC. Healthcare-associated infections. 2010. Available at: http://www.cdc.gov/HAI/burden.html. Accessed Jan. 21, 2013.

Megan E. Crosser is an infection preventionist at Banner Health, Sun City, Ariz. Sue E. Durkin is clinical nurse specialist, Advocate Good Samaritan Hospital, Downers Grove, Ill.